MiR-195 regulates mitochondrial function by targeting mitofusin-2 in breast cancer cells

Purohit, P. K., Edwards, R., Tokatlidis, K. and Saini, N. (2019) MiR-195 regulates mitochondrial function by targeting mitofusin-2 in breast cancer cells. RNA Biology, 16(7), pp. 918-929. (doi: 10.1080/15476286.2019.1600999) (PMID:30932749) (PMCID:PMC6546347)

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Abstract

Mitochondrial dynamics is a highly dysregulated process in cancer. Apoptosis and mitochondrial fission are two concurrent events wherein increased mitochondrial fragmentation serves as a hallmark of apoptosis. We have shown earlier that miR-195 exerts pro-apoptotic effects in breast cancer cells. Herein, we have demonstrated miR-195 as a modulator of mitochondrial dynamics and function. Imaging experiments upon miR-195 treatment have shown that mitochondria undergo extensive fission. We validated mitofusin2 as a potential target of miR-195. Which may provide a molecular explanation for the respiratory defects induced by miR-195 over-expression in breast cancer cells? Active, but not total, mitochondrial mass, was reduced with increasing levels of miR-195. We have further shown that miR-195 enhances mitochondrial SOD-2 expression but does not affect PINK1 levels in breast cancer cells. Collectively, we have revealed that miR-195 is a modulator of mitochondrial dynamics by targeting MFN2 thereby impairing mitochondrial function. Concomitantly, it enhances the scavenger of reactive oxygen species (SOD-2) to maintain moderate levels of oxidative stress. Our findings suggest a therapeutic potential of miR-195 in both ER-positive as well as ER-negative breast cancer cells.

Item Type:Articles
Additional Information:This work was supported by the Council of Scientific and Industrial Research, India [BSC0123];Newton Fund [269852058];Scottish Office Home and Health Department (GB) [WM120111];Biotechnology and Biological Sciences Research Council (GB) [BB/R009031/1)];Scottish Office Home and Health Department [HR07019)].
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tokatlidis, Professor Kostas and Edwards, Ruairidh
Authors: Purohit, P. K., Edwards, R., Tokatlidis, K., and Saini, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:RNA Biology
Publisher:Taylor & Francis
ISSN:1547-6286
ISSN (Online):1555-8584
Published Online:01 April 2019
Copyright Holders:Copyright © 2019 Informa UK Limited, trading as Taylor and Francis Group
First Published:First published in RNA Biology 16(7):918-929
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
769611Newton Bhabha PhD Placement 2016-2017Konstantinos TokatlidisBritish Council (UK) (BRCOU-UK)269852058RI MOLECULAR CELL & SYSTEMS BIOLOGY
624931Oxidative Folding and Redox Signalling in the Mitochondria Intermembrane Space.Konstantinos TokatlidisThe Royal Society (ROYSOC)WM120111RI MOLECULAR CELL & SYSTEMS BIOLOGY
3004020Mitochondria salvage via a novel antioxidant protein import pathwayKonstantinos TokatlidisBiotechnology and Biological Sciences Research Council (BBSRC)BB/R009031/1Institute of Molecular, Cell & Systems Biology
497261Scottish Universities Life Sciences Alliance (SULSA)- Translational BiologyJeremy MottramScottish Funding Council (SFC)HR07019III - PARASITOLOGY